Hydrophilic pressure sensitive hot-melt adhesives

ABSTRACT

A device for the release of substances from pressure sensitive hot-melt adhesives with a uniform or non-uniform distribution of said substances is characterized by the fact that the pressure sensitive hot-melt adhesive is hydrophilic and comprises at least one water-soluble, or at least water-swellable, polymer, at least one water-soluble, meltable adhesive resin, as well as substance to be released.

SPECIFICATION

The present invention relates to devices for the release of substancesfrom pressure sensitive hot-melt adhesives having an uneven or evendistribution of the substances.

Typical representatives of devices for the release of substances fromadhesives are self-adhesive products for the application on intact skin,for example, medicinal patches for the controlled dermal or transdermalrelease of substances and cosmetic patches for the release of active orodorous substances; self-adhesive products for the application oninjured skin, e.g., patches, wound dressings, or surgical films for therelease of substances to wounds.

Pressure sensitive adhesive layers comprising pharmaceutical or otheractive substances are for the most part formed by coating a solution ordispersion with subsequent evaporation of the solvent or dispersant.

The use of solvents or dispersing agents in the production of adhesivelayers for devices of the above-mentioned type is disadvantageous formany reasons; this applies to both the economic point of view because ofexpensive drying lines, extracting plants, recovery and disposalfacilities, and to the ecological point of view because of theenvironmental impact caused by solvents and dispersing agents as well astheir degradation products.

In contrast to this, adhesive layers manufactured from a melt of theformulation components have advantages with respect to economy andecology. However, there is the disadvantage that very high temperaturesare necessary to melt the commonly used pressure sensitive hot-meltadhesive formulations so that the pharmaceutical or other activesubstances to be incorporated are decomposed, modified or evaporated, atleast partially.

In addition, the conventional pressure sensitive hot-melt adhesiveformulations—as well as adhesive formulations bound by solvents ordispersants—have further disadvantages, in particular when used in man;in general, these become apparent in the form of skin reactions andpainful rubors during the application or after removal of the device.

In case of aggressively adhering devices, these skin irritations may bedue to an injury of the corneum when the adhesive device is removed fromthe skin. Most frequently, however, skin reactions result from the factthat the base components of adhesive formulations are of a lipophilicnature; this in particular applies to pressure sensitive adhesives. Whenapplied to the skin, these adhesives have the effect of occlusive filmsor foils which completely prevent the cutaneous respiration andevaporation of water and thus suppress the mechanisms ofthermoregulation at the application site. Since the water released bythe skin cannot evaporate, thin water films and water islands formbetween the adhesive layer and the skin and these represent an optimumenvironment for the growth and multiplication of skin germs. Once acertain population size is reached, the amount of skin germs decomposingper time unit is such that the concentration of toxic catabolic productsand decomposition products drastically increases, again resulting inmassive skin reactions.

There were attempts to combat these phenomena, e.g., in case of thepressure sensitive adhesive formulation for self-adhesive wounddressings, by incorporating so-called hydrocolloidal particles intopressure sensitive hot-melt adhesives, i.e., hydrophilic substances, inparticular polymers, which absorb and withdraw water from the surface ofthe skin.

But even these formulations cannot avoid another serious disadvantage ofconventional pressure sensitive hot-melt adhesives. In addition to theabove-mentioned, rather physical reasons resulting in skin irritations,it is first of all the allergic skin reactions that cause problems, andthese are usually caused by the chemical properties of the lipophilicadhesive resins used. Up to the present, this problem has not beensolved satisfactorily, since these adhesive resins cannot be omittedwhen a reliable adherence to the skin is required.

Owing to their lipophilic nature, prior art pressure sensitive hot-meltadhesive formulations for the release of substances have anotherdisadvantage: with respect to the controlled release of substances theyare suitable only for lipophilic substances. In the case of hydrophilicsubstances it is hardly possible to create the preconditions for therelease control relating to the thermodynamic activity in the pressuresensitive hot-melt adhesive. These substances must be dissolved in theadhesive formulation, at least partially, so that they can diffusewithin an adhesive formulation, reach the interface and be released; ingeneral, this cannot be achieved when hydrophilic substances andlipophilic pressure sensitive hot-melt adhesives are combined.

Accordingly, it was the object of the present invention to find a devicefor releasing substances from pressure sensitive hot-melt adhesives,which comprises a pressure sensitive hot-melt adhesive that reliablyadheres to the desired surface at room temperature after slightpressure, does not leave any residue on the surface after removal,absorbs cutaneous moisture, comprises non-allergenic adhesive resins,and permits the incorporation of hydrophilic substances in dissolvedform.

In a device for the release of substances from hydrophilic pressuresensitive hot-melt adhesives having an even or uneven distribution ofthese substances, this object is achieved with the present invention bythe fact that the pressure sensitive hot-melt adhesive is hydrophilicand comprises at least one water-soluble or at least water-swellablepolymer, at least one water-soluble, meltable adhesive resin, andsubstance to the released.

Most surprisingly, it turned out that it is possible to produce pressuresensitive hot-melt adhesives complying with the above-mentionedrequirements by combining water-soluble, or at least water-swellable,polymers with water-soluble, meltable adhesive resins under addition ofthe substances to be released; and in this connection water-soluble,meltable tacky substances, which are low-viscous and ropy per se—whencombined with hydrophilic polymers—form coherent layers of an excellentcohesion which, in addition to that, have adhesive forces absolutelycomparable to those of conventional adhesives.

Pressure sensitive hot-melt adhesives within the meaning of the presentinvention are those by means of which coated devices can reliably bejoined with surfaces at room temperature under slight pressure, andwhich have a cohesion permitting a residual-free removal of theadhesive-coated device from the application surface by simply strippingit off. In order to avoid undesired modifications of the substances tobe released or of other formulation components, the pressure sensitivehot-melt adhesives of the kind specified herein are preferably processedat temperatures between 40 and 150° C., most preferably at temperaturesbetween 80 and 120° C., in molten condition, and they solidify underformation of adhesive and cohesive forces.

Pressure sensitive hot-melt adhesives of the type mentioned hereindiffer greatly from hydrophilic, water-soluble adhesives known from theproduction of so-called gummed surfaces, e.g., envelopes or labels.These adhesives which build up cohesive but no adhesive forces aftermelting, processing, and setting are activated only when moistened withwater or saliva, and they are brought into contact with the applicationsurface in moist condition. After drying of the adhesive, adhesiveforces build up which firmly join the respective surfaces, e.g., paperlabels with glass surfaces. In contrast to surfaces joined by pressuresensitive hot-melt adhesives, said adhesive forces between device andsurface cannot be eliminated by simply pulling the adhesive-coateddevice off the application surface; in these cases neutralization of theadhesive forces can only be effected by redissolving or slightly solvingthe adhesive, e.g., by moistening with water, removal in a water-bath orover water vapor.

When formulating the pressure sensitive hot-melt adhesives according tothe present invention, the main problem was to find substances which arewater-soluble and meltable in addition, have adhesive properties at roomtemperature, and are known not to cause skin irritations or allergicreactions even in case of a prolonged application on human skin. Thesesubstances are very rare, and so far they are to be found in particularamong the natural substances. Such tackifying substances which,following the existing terminology, are referred to as adhesive resinspreferably are pantothenyl alcohol, honey, low-molecular sugars, such assaccharose, glucose and fructose, or derivatives of low-molecularsugars, such as saccharose acetate isobutyrate, as well as combinationsthereof.

Suitable water-soluble or water-swellable polymers within the meaning ofthe present invention include any hydrophilic natural, semi-synthetic orsynthetic polymer which melt at the applied temperatures or which—atleast partially—dissolve in dry or pre-swollen form in the adhesiveresin melts used. These preferably include gelatin, vegetablepolysaccharides, such as alginates, pectins, carrageenans, or xanthan;cellulose derivatives, such as methyl cellulose, hydroxypropylcellulose,hydroxyethylcellulose, hydroxypropyl methylcellulose, or sodiumcarboxymethylcellulose; starch and starch derivatives, galactomannan andgalactomannan derivatives, polyvinyl alcohol, polyvinylpyrrolidone,vinyl-pyrrolidone-vinyl-acetate-copolymers, polyethylene glycols, andpolypropylene glycols.

In connection with the present invention, the term “substances” is to beunderstood as chemical elements, organic and inorganic compounds which,in a generic device, are capable of migrating out of the componentscomprising them, thus causing a desired effect. Among the fields ofapplication of the device according to the present invention, human andveterinary medicine, as well as the application to plants are of specialimportance, with an embodiment of the present invention in the form of apatch being particularly preferred.

The device according to the present invention for the release ofsubstances from pressure sensitive hot-melt adhesives is applied, forexample, on intact skin or on wounds. In these cases the substances tobe released preferably serve the dermal treatment of topical skindiseases, the intradermal or transdermal treatment of diseases, thetreatment of wounds, or the skin care in cosmetic preparations.

For the dermal treatment of local skin diseases the following substancesare used: local anaesthetics, local antibiotics, antiseptics,antimycotics, antihistaminics, and antipruritic drugs; keratolytics andcaustic drugs; virustatics, antiscabietic agents, steroids, as well asdifferent substances for the treatment of acne, psoriasis, orphotodermatoses. Active substances applied intradermally include, forexample, steroid and non-steroid antirheumatics, local anaesthetics,substances stimulating the blood flow, or vasoprotectors andvasoconstrictors for the treatment of vascular diseases, as well asactive substances to influence the processes in the subcutaneous fattytissue. The active substances applied transdermally include, forexample, neuroleptics, antidepressants, tranquilizers, hypnotics,psychostimulants, analgesics, cytostatic drugs, hormones, musclerelaxants, antiparkinson drugs, ganglionic blockers, sympathomimetics,alpha-sympatholytics, betasympatholytics, antisympathotonics,antidiabetics, coronary therapeutic agents, antihypertensives,anti-asthmatics, diuretics, or active substance for weight reduction.

For the treatment of wounds styptic active substances are used, forexample, collagen, wound-cleansing substances, such as enzymes,antiseptics, disinfectants, and antibiotics; pain-relieving agents andanaesthetic active substances, as well as active substances promotingwound healing to stimulate granulation, to induce vascularization, or topromote epithelization.

In a preferred embodiment for the transdermal application, thehydrophilic pressure sensitive hot-melt adhesive comprisesactetylsalicylic acid, preferably for the antithrombotic therapy, i.e.,for the prevention of a first cardiac infarction, for the prevention ofa recurrent infarction, for the treatment of unstable angina pectoris,for the thrombosis prophylaxis after transplantation of vascularprotheses or artificial heart valves, for the thrombosis prophylaxis ofthe peripheral arterial vessels, as well as for the thrombosisprophylaxis of cerebral inadequate circulation.

According to another preferred embodiment for the transdermalapplication, the hydrophilic pressure sensitive hot-melt adhesivecomprises a steroid hormone, preferably estradiol; when appliedtransdermally this is used for hormone substitution during thepostmenopause or for the treatment of osteoporosis. On the other hand, adevice for the release of estradiol from hydrophilic pressure sensitivehot-melt adhesives may also be applied on long-term wounds, for instancecrural ulcera, for the treatment of wounds.

In a preferred embodiment for the intradermal application of activesubstances, the hydrophilic pressure sensitive hot-melt adhesivecomprises an eutectic mixture of the local anaesthetics, lidocaine andprilocaine. Both in the intradermal analgesia, for example prior tovenipunctures, and in the treatment of rheumatoid arthritis, this activesubstance mixture may achieve an effect which cannot be obtained bymeans of the conventionally used active substances and active substancecombinations from the group of topical anaesthetics.

According to another preferred embodiment of the device according to thepresent invention, the hydrophilic pressure sensitive hot-melt adhesivecomprises vegetable preparations, e.g., extracts or tinctures. These maybe used for the treatment of topical skin diseases, for example, oakbark extract, walnut extract, tincture of arnica, hamamelis extract,ribwort extract, pansy extract, thyme or sage extract; for the treatmentof damaged or injured skin, for example, St. John's wort tincture, coneflowers tincture, chamomile flowers extract, or calendula flowerstincture; and for the care of exhausted and damaged skin, for example,birch leaves extract, nettle extract, coldsfoot extract, comfreytincture, horsetail extract, or aloe vera extract. Vegetablepreparations may also be released from hydrophilic pressure sensitivehot-melt adhesives for the intradermal treatment of diseases, forexample, extracts of horse chestnut and butcher's broom in case of veindiseases, or extracts and tinctures of arnica, calendula, and capsicumin case of contusions, distortions, or haemorrhages. Vegetablepreparations in hydrophilic pressure sensitive hot-melt adhesivesaccording to the present invention may also be used in the transdermaltherapy, for example, ginseng extract in case of geriatric complaints;valerian tincture, extracts of melissa and hop to cause a sedativeeffect in case of superexcitation, sleep disturbances, and stress;extracts of kola and tea to achieve a stimulative effect; or hawthornextract for the stabilization of the circulatory system.

In particular cases where the formulation components of the hydrophilicpressure sensitive hot-melt adhesive themselves are capable ofextracting ingredients from parts of plants, the hydrophilic pressuresensitive hot-melt adhesive may also comprise triturated plant portions.According to a preferred embodiment, the hydrophilic pressure sensitivehot-melt adhesive of the device according to the present inventioncomprises tobacco powder. Such a device can be used by smokers as analternative to tobacco, cigarettes or similar tobacco products. Thissubstitute, e.g., for cigarettes, offers the advantage that the smokerhimself does not inhale the injurious substances resulting during thecombustion of tobacco without having to dispense with the desiredeffects of tobacco consumption, on the one hand, and that nonsmokers arenot subjected to the risks of passive smoking, on the other hand.

The device according to the present invention for the release ofsubstances from hydrophilic pressure sensitive hot-melt adhesives mayalso be used on plants. For instance, superficial, locally limited plantdiseases can be treated with active substances which are released fromthe hydrophilic pressure sensitive hot-melt adhesive to the plantsurface. Also, active substances having a systemic effectiveness, whichserve the protection of the plant from pathogenic agents and pests orthe treatment of plants after infection and existing infestation, orwhich serve the growth control or the nutrition of the plant, can bereleased from the hydrophilic pressure sensitive hot-melt adhesive tothe plant surface, e.g., to the leaves, the stem, or the roots. Afterrelease from the hydrophilic pressure sensitive hot-melt adhesive, theactive substance penetrates into epidermal and subepidermal tissues ofthe plant, enters the transport systems of the plant, and is distributedin the plant systemically after absorption.

The systemic active substances may, for example, be fungicides, such asbitertanole, fenarimole, triforine, aluminiumfosetyl, or tridemorph;insecticides, such as nicotine, demeton, dimethoate, fenthion, ormenazon; or plant hormones, such as auxins, gibberellins, cytokinins, orabscisic acid.

The base formulation and production of the device according to thepresent invention for the release of substances from pressure sensitivehot-melt adhesives with a uniform or non-uniform distribution of thesubstances, according to the features of the main claim are exemplifiedin the following:

EXAMPLE 1

100 parts of the water-soluble adhesive resin, pantothenyl alcohol, aremelted at 70° C. 30 parts of polyethylene glycol having a molecularweight of 15,000 are slowly stirred into the melt until a clear meltresults.

10 parts of sodium alginate and 1.5 parts of substance to be released,e.g., lidocaine hydrochloride, are slowly stirred into the melt until aneven distribution is achieved.

Then, the pressure sensitive hot-melt adhesive is spread on a suitablesubstrate, e.g., a siliconized paper composite, by means of knifecoating.

After cooling, a suitable backing layer, e.g., a thin polyester sheet,is laminated on the pressure sensitive hot-melt adhesive. Devices ofdesired size are punched from this laminate.

The pressure sensitive, hydrophilic contact adhesive of the deviceaccording to the present invention thus manufactured has an excellentinitial tackiness when applied to the skin, an excellent adhesion duringthe wearing duration, and an excellent cohesion when stripped off theskin so that the device can be removed from the skin without leaving anyresidue. In addition, the device stands out for the fact that thehydrophilic pressure sensitive hot-melt adhesive absorbs cutaneousmoisture, prevents the formation of water films promoting the growth ofbacteria, does not cause any skin irritations or allergic reactions,and—owing to the absorption of cutaneous moisture—that it is soft andsupple at the interface to the skin, permitting an easy and painless,residue-free removal from the skin without causing any damage to thecorneum.

According to another preferred embodiment of the device according to thepresent invention for the release of substances from pressure sensitivehot-melt adhesives, said hydrophilic pressure sensitive hot-meltadhesive comprises 0.1% to 40% of water to influence the thermodynamicactivity of the substance to be released.

EXAMPLE 2

20 parts of pantothenyl alcohol are melted at 90° C.; 10 parts ofglycerol, 2 parts of Tween 20, 2 parts of ethylcellulose, and 1.5 partsof estradiol are slowly stirred into the melt until an even distributionis achieved (melt A).

18 parts of gelatin, 10 parts of polyvinyl pyrrolidone, 5 parts ofsodium carboxymethylcellulose, and 11.5 parts of saccharose are madeinto a paste at room temperature using 20 parts of water, intensivelyhomogenized up to an even distribution, and then heated to 90° C. understirring (melt B).

Melt B is slowly stirred into melt A at 90° C. until a uniformdistribution is achieved. Then, the pressure sensitive hot-melt adhesiveis spread on a siliconized paper composite by means of a coating knife;after cooling, a polyester sheet is laminated thereon. Devices of thedesired area are punched out of this laminate.

When applied to the skin, the pressure sensitive, hydrophilic hot-meltadhesive of the device according to the present invention thusmanufactured meets the above-mentioned requirements with respect toinitial tackiness, adherence during wearing, cohesion, absorption ofcutaneous moisture, and the property of not irritating the skin. Inaddition, it has the advantage that—as compared to the known lipophilictransdermal systems—the thermodynamic activity of estradiol in theadhesive layer is significantly influenced due to the presence of water.This extends the possibilities of influencing and controlling theestradiol release from such a device. In addition, owing to thehydrophilic character, the described formulation has the advantage thatwhen—used for the release of estradiol or other substances to wounds—aninteraction with the wound exudate is possible, on the one hand, andthat, on the other hand, the presence of water in the formulationcreates a moist microclimate in the wound which promotes the healingprocesses in case there is no wound exudation.

According to another preferred embodiment of the device according to thepresent invention for the release of substances from pressure sensitivehot-melt adhesives, the hydrophilic pressure sensitive hot-melt adhesivecomprises a lipophilic phase in order to influence the thermodynamicactivity of the substance to be released.

EXAMPLE 3

27 parts of pantothenyl alcohol are melted at 90° C. 12.5 parts ofsodium alginate, 12.5 parts of gelatin, and 1 part of chlorophyll areslowly stirred into the melt until a uniform distribution is achieved(melt A).

Separately, 25 parts of hydroabietyl alcohol are melted at 125° C. 10parts of an ethylene-vinyl-acetate-copolymer having a vinyl acetatecontent of 28%, 10 parts of a polyalkadiene having a monomer chainlength of C4 to C5 , and 2 parts of lidocaine are slowly stirred intothe hydroabietyl alcohol melt at 120° C. until a clear melt results(melt B).

Melt B is cooled to 90° C. under stirring; at 90° C. it is slowlystirred into melt A up to a uniform distribution. The pressure sensitivehot-melt adhesive is then spread on a siliconized paper composite bymeans of knife coating. After cooling, a polyester sheet is laminatedthereon, and devices of desired size are punched from the laminate.

When applied to intact skin or wounds, the pressure sensitive,hydrophilic hot-melt adhesive of the device according to the presentinvention such manufactured—like the above-described device—meets thementioned requirements with respect to initial tackiness, adhesionduring wearing, cohesion, non-irritancy to the skin, and absorption orinteraction with the wound exudate or cutaneous moisture.

The advantage of combining the hydrophilic base components of the deviceaccording to the present invention with lipophilic formulationcomponents in a hydrophilic pressure sensitive hot-melt adhesive lies inthe fact that even lipophilic substances which are to be released fromthe pressure sensitive hot-melt adhesive are present in an at leastpartially dissolved form; this is an important condition for thediffusion of the substance in the pressure sensitive hot-melt adhesiveand thus for the release from the pressure sensitive hot-melt adhesive.

The lipophilic phase of the device according to the present inventionmay be non-separated and coherent, as in the above Example; however, itmay also be present in a separated and incoherent state in the form ofsmall particles or droplets.

Homo-, co- or block polymers may be used as components of the lipophilicphase, e.g., polyamides, polyesters, polycaprolactams, polycaprolactone,ethylene-vinyl-acetate copolymers (EVA), ethylene-ethyl-acrylatecopolymers (EEA), polyvinyl ether, poly(meth)acrylates, polyvinylacetals, polyvinyl acetates, styrenebutadiene-block polymers, isopreneblock polymers, polyurethanes, ethylcellulose,cellulose-acetate-butyrate, synthetic rubbers (e.g. neoprene rubber),polyisobutylene, butyl-rubber, and acrylonitrile-butadiene copolymers orresins, such as epoxide resins, melamine resins, phenolformaldehyderesins, and resorcinolformaldehyde resins; among others the followingmodified resins may also be used: hydrogenated colophony, polymerizedcolophony, dimerized resin acids, disproportionated colophony, methylesters of colophony, glycerol esters of hydrogenated colophony, methylesters of hydrogenated colophony, pental esters, triethylene glycolesters of hydrogenated colophony, hydroabietyl alcohol and itsderivatives, glycerol esters, di-triol esters, and pental esters ofresin acids, pental esters of polymerized colophony, pental esters ofdimerized colophony, glycerol esters of dimerized colophony, esters ofcolophony modified with maleic acid or phenol, aromatic and aliphatichydrocarbon resins, hydrogenated resins, polyterpene resins and modifiedterpene resins.

However, the lipophilic phase may also consist of natural, semisyntheticor synthetic fats and oils, such as olive oil, castor oil, peanut oil,soy bean oil, linseed oil, sesame oil, jojoba oil, avocado oil,hydrogenated peanut oil, hydrogenated castor oil, triglyceride mixtures(Miglylol®, Softisan®), or silicone oils; natural, semisynthetic orsynthetic waxes, such as beeswax, wool wax, earth wax, spermaceti, oleicacid oleyl ester, isopropyl palmitate, isopropyl myristate, ethyloleate, cetyl palmitate, or cetyl stearate; fatty alcohols, such asdodecyl alcohol or cetyl alcohol; fatty acids, such as myristic acid,oleic acid, or linoleic acid; propoxylated, ethoxylated or sulfatedfatty alcohols, fatty acid alkyl amides, fatty acid-protein-condensationproducts, phospholipids, sterols, or hydrocarbons, such as paraffins orparaffin oils. If the lipophilic phase is present in separated form,adjuvants, such as emulsifiers and/or protective colloids, are added tothe preparation according to the present invention in order to stabilizethe disperse phase.

In addition to the above-mentioned adjuvants, the device for the releaseof substances from hydrophilic pressure sensitive hot-melt adhesives maycomprise as adjuvants:

humectants, such as glycerol, sorbitol, polyethylene glycol,polypropylene glycol,

softening agents, such as citric acid ester, tartaric acid ester, orglycerol ester,

penetration enhancers, such as alkyl sulfates, alkyl sulfonates, alkalisoaps, fatty acid salts of multivalent metals, betaines, amine oxides,fatty acid esters, mono-, di- or triglycerides, long-chain alcohols,sulfoxides, nicotinic acid ester, salicylic acid, N-methyl pyrrolidone,2-pyrrolidone, or urea,

preservatives, such as p-Cl-m-cresol, phenylethyl alcohol, phenoxyethylalcohol, chlorobutanol, 4-hydroxybenzoic acid methylester,4-hydroxybenzoic acid propylester, benzalkonium chloride,cetylpyridinium chloride, chlorohexidine diacetate or gluconate,ethanol, or propylene glycol,

disinfectants, for example, halogens, such as polyvidoneiodine; halogencompounds, such as sodium hypochloride or tosylchloride sodium;oxidants, such as hydrogen peroxide or potassium permanganate, arylmercury compounds, such as phenylmercury borate or merbromin; alkylmercury compounds, such as thiomersal; organotin compounds, such astri-n-butyltin benzoate; silver protein compounds, such as silverprotein acetyltannate; alcohols, such as ethanol, n-propanol, orisopropanol; phenols, such as thymol, o-phenylphenol,2-benzyl-4-chlorophenol, hexachlorophene, or hexylresorcinol; or organicnitrogen compounds, such as 8-hydroxyquinoline, chloroquinaldol,clioquinol, ethacridine, hexetidine, chlorohexidine, or ambazone,

pH-regulators, such as glycerol buffers, citrate buffers, boratebuffers, phosphate buffers, or citric acid phosphate buffers,

antioxidants, such as ascorbic acid, ascorbic palmitate, tocopherolacetate, propyl gallate, butylhydroxyanisole, or butylatedhydroxytoluene,

active substance stabilizers, such as mannitol, glucose, lactose,fructose, saccharose,

odorous substances, dyes, cleaning agents, substances for personalhygiene,

emulsion stabilizers, such as non-ionogenic emulsifiers, amphotericemulsifiers, cation-active emulsifiers, and anion-active emulsifiers,

fillers, such as micro-crystalline cellulose, aluminum oxide, zincoxide, titanium oxide, talcum, silicon dioxide, magnesium silicate,magnesium aluminum silicate, kaolin, hydrophobic starch, calciumstearate, or calcium phosphate.

In addition to the knife coating procedures mentioned in the aboveExamples, processing of the active substance-releasing, hydrophilicpressure sensitive hot-melt adhesive layer may also be effectedaccording to other methods known to those skilled in the art, e.g., rollcoating, extrusion, casting, spraying, or printing. In many of theseprocesses the limit of processibility of the hydrophilic pressuresensitive hot-melt adhesives is achieved at a viscosity in the range ofabout 80,000 Pa.

In case the support to be treated with the adhesive—a component of thedevice—could be damaged by the temperature of the adhesive which isapplied in hot condition—be it by decomposition, reaction, or partialmelting—a cooled support may be used. Cooling may be effected accordingto methods known per se, for instance, introduction of cold, inert gasesor contact with a cooling surface.

When highly volatile and/or thermally instable substances are to bereleased, the following special measures may be suitable for processing:

A: Working at the lowest possible temperatures

B: Increasing the external pressure in order to decrease evaporation

C: Saturation of the vapor chamber above the melt with the vaporoussubstance

D: Working with the lowest possible amount of volatile substance in themelt, according to the instructions.

It goes without saying that these measures, for instance, working in anencapsulated unit, are limited by the laws known to the skilled artisan,both with respect to the intended use of the device to be manufacturedand to the material conditions.

Devices according to the present invention wherein the activesubstance-releasing portion of the device comprises hydrophilic pressuresensitive hot-melt adhesives may be built-up according to any patchconstruction known to those skilled in the art. Basic types of suchconstructions include, for example, the membrane system and the matrixsystem.

A membrane system comprises at least 5 parts: a flexible backing layer,an active substance-containing, pressure sensitive hot-melt adhesive, amembrane for controlling the active substance release, an adhesive layerlaminated on said membrane for fixing the system to the skin, as well asa removable protective layer covering the adhesive surface of the patchfacing the skin. A matrix system (FIG. 1) of the most simple typecomprises three parts: a flexible backing layer, an activesubstance-containing, hydrophilic pressure sensitive hot-melt adhesive,and a removable protective layer which covers the adhesive surface ofthe device facing the skin.

A process for the production of a device according to the presentinvention of the type matrix system comprises continuous ordiscontinuous application of molten, hydrophilic pressure sensitivehot-melt adhesive, which comprises the substance to be released, at atemperature of the pressure sensitive hot-melt adhesive between 40 and150° C., preferably 80 to 120° C., onto a flexible backing layer, andoptional provision of the protective layer material.

Another process comprises continuous or discontinuous application ofmolten, hydrophilic pressure sensitive hot-melt adhesive, whichcomprises the substance to the released, at a temperature of thepressure sensitive hot-melt adhesive between 40 and 150° C., preferably80 to 120° C., onto a protective layer material, and optional provisionof the flexible backing layer. The hydrophilic pressure sensitivehot-melt adhesive may be applied to the protective layer or backinglayer, for example, in the form of layers or in individual regionsaccording to a predetermined pattern.

Suitable materials for the flexible backing layer include, for example,polyester, polyamide, polyethylene, polypropylene, polyurethane,polyvinyl chloride, both as so-called “solo-films” and as sandwich filmsin a combination of films of different of these plastic materials. Inaddition, these sheets may be aluminized or laminated with an aluminumfoil.

Suitable materials for the removable protective layer include, forexample, polyester, polyethylene, polypropylene, and papers coated withsaid materials and optionally aluminized or laminated with an aluminumfoil. Additionally, the films or papers are coated with silicone inorder to render them removable.

Depending on the intended use, for example, when the substance to bereleased is to be delivered through the backing layer, e.g., in case ofessential oils, the pressure sensitive hot-melt adhesive may be providedwith a backing layer which is permeable to the substance/s to bereleased; whereas a backing layer which is impermeable to the substanceto be released is preferred in the embodiment of the device as atransdermal system where the substance is to be released to the skinonly.

During the melting of the formulation components of the hydrophilicpressure sensitive hot-melt adhesive air may be stirred into the mass sothat the hydrophilic pressure sensitive hot-melt adhesive obtained afterspreading or casting will have a porous structure. The production andstabilization of the porous structure may be supported, for example, byadding foaming agents, such as saponins, alginic esters, amine oxides,or fatty amine oxides.

The composition of the device according to the present invention as awhole or that of the hydrophilic pressure sensitive hot-melt adhesivemay be chosen such that the hydrophilic pressure sensitive hot-meltadhesive be biodegradable. Biodegradability is meant to be understood,for example, as the effect of UV-light, the action of microbes, or theaction of enzymes.

The device according to the present invention as well as the hydrophilicpressure sensitive hot-melt adhesive may have a multilayer structure.For instance, at least two hydrophilic pressure sensitive hot-meltadhesives may be joined according to known methods to form a composite(FIG. 2). It is also possible to join one or more hydrophilic pressuresensitive hot-melt adhesives with one or more lipophilic elements toform a composite of any structure desired (FIGS. 3/4). For example, suchelements may serve as controlling elements, storing elements, permeableor impermeable separating elements. The individual elements of thecomposite may be a coherent, interconnected unit; they may also beseparated into segments which are surrounded or enclosed by the elementlying above or below (FIGS. 5/6). For instance, a lipophilic adhesivelayer may be applied to a hydrophilic pressure sensitive hot-meltadhesive either continuously or in the form of points or diamonds,wherein the pressure sensitive hot-melt adhesive may fill the spacesbetween the lipophilic segments (FIG. 7). According to anotherembodiment, the hydrophilic pressure sensitive hot-melt adhesive iscombined with textile fabrics, fibrous structures, and/or natural orsynthetic foams. In this multi-layer composite the individual layers maybe produced separately according to known methods and then be joined.The layers may also penetrate each other, for example, when the moltenmass of the hydrophilic pressure sensitive hot-melt adhesive is appliedon a fabric, fibrous structure, or foam prior to the formation of thefilm, and the formation of the film takes place only after the mass hasbeen soaked into the fabric or the foam.

Fixation of the device according to the present invention at the placeof use is generally effected by the hydrophilic pressure sensitivehot-melt adhesive of the device. Another possibility of fixing thedevice according to the present invention to the place of application isthat the backing layer has larger dimensions than the part consisting ofhydrophilic pressure sensitive hot-melt adhesive and that at least theprojecting portions of the backing layer are provided with an additionaladhesive layer (FIG. 8).

The last-mentioned embodiments of the device according to the presentinvention wherein the hydrophilic pressure sensitive hot-melt adhesiveis present in a multi-layer, multi-part form or in combination withseparating and controlling elements, have the advantage that parts ofdifferent composition may be combined with each other. The use ofdifferent adjuvants or different active substance concentrations in theindividual elements shall provide a release behavior of the activesubstance/s which is required for the application and that cannot beachieved, for example, by a single-layer structure of the hydrophilicpressure sensitive hot-melt adhesive.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 to 8 illustrating the invention will be described in more detailin the following:

FIG. 1 represents a hydrophilic pressure sensitive hot-melt adhesive (1)provided with an impermeable backing layer (2) on one side and with aremovable, impermeable protective layer (3) on the opposite side.

FIG. 2 illustrates a multi-layer, hydrophilic pressure sensitivehot-melt adhesive (laminate) wherein the hydrophilic pressure sensitivehot-melt adhesive (1) is divided into two layers (1′, 1″) .

FIG. 3 shows the active substance-containing, pressure sensitivehot-melt adhesive (1); the side facing the substrate is combined with alipophilic element (4) which does not contain any active substance andserves as controlling membrane.

FIG. 4 also shows a multi-layer composite wherein an activesubstance-containing, hydrophilic pressure sensitive hot-melt adhesive(1) is enclosed in a sandwich-type manner by two lipophilic elements(4′, 4″). Again, this arrangement is covered by backing layer (2) andprotective layer (3).

FIGS. 5a and 5 b show an embodiment of the hydrophilic pressuresensitive hot-melt adhesive (1), wherein it is surrounded by alipophilic element (4) at least partially, or wherein it surrounds alipophilic element at least partially. Both elements may comprise activesubstances.

FIG. 6a shows another embodiment wherein the hydrophilic pressuresensitive hot-melt adhesive (1) acting as an active substance-containingcontrolling element encloses an additional lipophilic active substancestorage (4); in

FIG. 6b, the hydrophilic pressure sensitive hot-melt adhesive (1) actingas storing element is completely embedded in a lipophilic film (4)acting as controlling element; one surface of the lipophilic storingelement (4) or of the pressure sensitive hot-melt adhesive (1) acting asstorage may also be immediately adjacent to the backing layer (2) (FIGS.6c and 6 d).

FIGS. 7a, 7 b, and 7 c represent embodiments of a hydrophilic pressuresensitive hot-melt adhesive (1) having an adhesive layer (5); saidadhesive layer covers the whole hydrophilic pressure sensitive hot-meltadhesive continuously (FIG. 7a), or discontinuously, i.e., in aninterrupted manner (FIG. 7b), or parts of the hydrophilic pressuresensitive hot-melt adhesive (FIG. 7c).

FIGS. 8a and 8 b show devices wherein a hydrophilic pressure sensitivehot-melt adhesive (1) is covered with a protective layer (3) and abacking layer (2) which has larger dimensions than the hydrophilicpressure sensitive hot-melt adhesive (1) and which is completely (FIG.8a) or partially (FIG. 8b) coated with an adhesive film (5).

In addition to the already presented Examples 1 to 3 which basicallydescribe the device according to the present invention for the releaseof substances from hydrophilic pressure sensitive hot-melt adhesives,the following Examples are meant to describe formulation alternatives,embodiments and application possibilities of the device mentioned in themain claim; however, this listing can by no means be extensive:

EXAMPLE 4

25 parts of pantothenyl alcohol are melted at 90° C. 10 parts of sodiumalginate and 10 parts of gelatin are slowly stirred into the melt untila uniform distribution is achieved (melt A).

25 parts of hydroabietyl alcohol are melted separately at 125° C. 10parts of an ethyl-vinyl acetate-copolymer having a vinyl acetate contentof 28%, 10 parts of a polyalkadiene having a monomer chain length of C4to C5, and 10 parts of acetylsalicylic acid are slowly stirred into thehydroabietyl alcohol melt at 120° C. until a clear melt results (meltB).

Melt B is cooled to 90° C. under stirring; at 90° C. it is slowlystirred into melt A until a uniform distribution is achieved. Thepressure sensitive hot-melt adhesive is then spread on a siliconizedpaper composite at a mass per unit area of 300 g/m² by means of knifecoating. After cooling, a polyester sheet is laminated thereon, anddevices having an area of 30 cm² are punched from the laminate; thedevices contain 90 mg of acetylsalicylic acid.

EXAMPLE 5

20 parts of pantothenyl alcohol are melted at 90° C. 10 parts ofglycerol, 4 parts of ethylcellulose, 4 parts of lidocaine, and 4 partsof prilocaine are slowly stirred into the melt up to an evendistribution (melt A).

At room temperature, 18 parts of gelatin, 10 parts ofpolyvinylpyrrolidone, 5 parts of sodium carboxymethyl starch, and 5parts of saccharose are made into a paste with 20 parts of water,homogenized intensively until an even distribution is achieved, and thenheated to 90° C. under stirring (melt B).

At 90° C., melt B is slowly stirred into melt A up to a uniformdistribution. The pressure sensitive hot-melt adhesive is then spread ata mass per unit area of 500 g/m² on a siliconized paper composite bymeans of knife coating. After cooling, a polyester sheet is laminatedthereon. Devices having a surface of 25 cm² are punched from thislaminate; the devices comprise 50 mg of lidocaine and 50 mg ofprilocaine.

EXAMPLE 6

25 parts of pantothenyl alcohol are melted at 90° C. 12.5 parts ofsodium alginate and 12.5 parts of gelatin are slowly stirred into themelt until a uniform distribution is achieved (melt A).

Separately, 25 parts of hydroabietyl alcohol are melted at 125° C. 10parts of an ethylene-vinyl acetate-copolymer having a vinyl acetatecontent of 28%, 10 parts of a polyalkadiene having the monomer chainlength C4 to C5, 2.5 parts of lidocaine, and 2.5 parts of prilocaine areslowly stirred into the hydroabietyl alcohol melt at 120° C. until aclear melt results (melt B). Under stirring to 90° C., melt B is slowlystirred into melt A up to a uniform distribution. The pressure sensitivehot-melt adhesive is then spread on a siliconized paper composite at amass per unit area of 500 mg/m² by means of knife coating. Aftercooling, a polyester sheet is laminated thereon, and devices having anarea of 25 cm² are punched from the laminate; the devices comprise 31.25mg of lidocaine and 31.25 mg of prilocaine.

EXAMPLE 7

20 parts of pantothenyl alcohol are melted at 90° C. 10 parts ofglycerol, 1 part of ethylcellulose, and 5 parts of tobacco powder areslowly stirred into the melt until an even distribution is achieved(melt A).

At room temperature, 18 parts of gelatin, 10 parts ofpolyvinylpyrrolidone, 5 parts of sodium carboxymethyl starch, and 11parts of saccharose are made into a paste using 20 parts of water,homogenized intensively until an even distribution is achieved, and thenheated to 90° C. under stirring (melt B).

At 90° C., melt B is slowly stirred into melt A up to a uniformdistribution. The pressure sensitive hot-melt adhesive is then spread ata mass per unit area of 600 g/m² on a siliconized paper composite bymeans of knife coating. After cooling, a polyester sheet is laminatedthereon. Devices having an area of 20 cm² are punched from thislaminate; the devices comprise 60 mg of tobacco powder.

EXAMPLE 8

50 parts of pantothenyl alcohol are melted at 90° C. 25 parts ofpolyethylene glycol having a molecular weight of 15,000, 20 parts ofsodium alginate, and 5 parts of an aqueous chlorohexidine digluconatesolution are slowly stirred into this melt until an even distribution isachieved.

Then, the pressure sensitive hot-melt adhesive is spread on asiliconized paper composite at a mass per unit area of 300 g/m² by meansof knife coating. After cooling, a polyester sheet is laminated thereon.Devices having an area of 200 cm² and containing 300 mg chlorohexidinedigluconate solution are punched from this laminate. The device is usedtopically for the disinfection of the skin in case of bacterially causedskin diseases or for the disinfection of infected wounds.

EXAMPLE 9

20 parts of pantothenyl alcohol are melted at 90° C. 16 parts of sodiumalginate, 9 parts of salicylic acid, and 2 parts of ethylcellulose arestirred into the melt until an even distribution is achieved (melt A).

Separately, 28 parts of hydroabietyl alcohol, 15 parts of anethylene-vinyl-acetate copolymer having a vinyl acetate content of 28%,and 10 parts of a polyalkadiene having a monomer chain length of C4 toC5 are melted at 125° C. (melt B).

Melt B is cooled to 90° C. under stirring; at 90° C. it is slowlystirred into melt A until a uniform distribution is achieved. Thepressure sensitive hot-melt adhesive is then spread on a siliconizedpaper composite at a mass per unit area of 1,400 g/m² by means of acoating knife; prior to cooling, an open-cell polyurethane foam of 2 mmthe back of which is sealed with a polyurethane sheet of a thickness of20 μm is placed on the still soft mass under slight pressure.

After cooling, oval devices having an area of 15 cm² are punched fromthis composite. Because of the keratolytic action of the salicylic acidcontained in the pressure sensitive hot-melt adhesive, these devicescomprising a pressure-sensitive-hot-melt-adhesive-foam-composite areused, for example, for the topical treatment of corns. The combinationwith foam simultaneously reduces the pressure on the site to thetreated.

EXAMPLE 10

20 parts of pantothenyl alcohol are melted at 90° C. 10 parts ofglycerol and 1 part of ethylcellulose are slowly stirred into the meltup to an even distribution (melt A).

At room temperature, 18 parts of gelatin, 10 parts ofpolyvinylpyrrolidone, 5 parts of sodium carboxymethyl starch, 10 partsof saccharose, 2 parts of St. John's wort tincture, 2 parts of coneflower tincture, and 2 parts of chamomile extract are made into a pasteusing 20 parts of water, intensively homogenized until an evendistribution is obtained, and then heated to 90° C. under stirring (meltB).

At 90° C., melt B is slowly stirred into melt A until an evendistribution is achieved. Then, the pressure sensitive hot-melt adhesiveis spread on a siliconized HDPE-film at a mass per unit area of 600 g/m²by means of knife coating; after cooling, a polyester sheet is laminatedthereon. Circular pieces having an area of 10 cm² are punched from thispressure sensitive hot-melt adhesive-polyester-composite. The polyesterside of these pieces is laminated on the adhesive layer of anacrylate-coated polyester sheet. After removal of the siliconizedHDPE-film, a siliconized paper composite is laminated thereto; circulardevices having an area of 25 cm² are punched such that the hydrophilicpressure sensitive hot-melt adhesive is in a central position, in themiddle of the device. Thus, the device consists of a backing layer ofpolyester, an adhesive layer for fixation on the skin, a separatinglayer of polyester to prevent migration of substances from thehydrophilic pressure sensitive hot-melt adhesive into the lipophilicadhesive layer, the tincture- or extract-containing hydrophilic pressuresensitive hot-melt adhesive, and a protective layer to be removed priorto application.

The device is used locally, for example, for the treatment offirst-degree burns, contused lesions, and slow-healing, superficialwounds.

EXAMPLE 11

18 parts of pantothenyl alcohol are melted at 90° C. 8 parts of glyceroland 4 parts of ethylcellulose are slowly stirred into the melt until aneven distribution results (melt A).

20 parts of gelatin, 10 parts of polyvinylpyrrolidone, 5 parts of sodiumcarboxymethyl starch, 10 parts of saccharose, and 5 parts of a 4%collagen dispersion are made into a paste at room temperature with 20parts of water, intensively homogenized up to a uniform distribution,and then heated to 90° C. under stirring (melt B).

At 90° C., melt B is slowly stirred into melt A up to an evendistribution. The pressure sensitive hot-melt adhesive is then spread ona siliconized paper composite at a mass per unit area of 1,500 g/m² bymeans of knife coating; after cooling, a polyurethane sheet is laminatedthereon. Devices of 100 cm² are punched from the laminate; they comprise30 mg of pure collagen. The device is used for the release of thehealing-promoting collagen from the hydrophilic pressure sensitivehot-melt adhesive to slow-healing problematic wounds, e.g., varicoseulcera.

EXAMPLE 12

20 parts of pantothenyl alcohol are melted at 90° C. 18 parts of sodiumcarboxymethylcellulose are slowly stirred into the melt up to an evendistribution (melt A).

32 parts of hydroabietyl alcohol are melted separately at 125° C. 16parts of an ethylene-vinyl-acetate-copolymer having a vinyl acetatecontent of 28%, 10 parts of a polyalkadiene having a monomer chainlength of C4 to C5, 2 parts of ethylcellulose, 1 part of chamomile oil,and 1 part of chlorophyll are slowly stirred into said hydroabietyl meltat 120° C. until a clear melt results (melt B).

Melt B is cooled under stirring to 90° C. and slowly stirred into melt Aat 90° C. up to an even distribution. Then, the pressure sensitivehot-melt adhesive is spread on a siliconized paper composite at a massper unit area of 1,000 g/m² by means of knife coating. After cooling, apolyurethane sheet is laminated thereon. Devices having an area of 25cm² are punched from the laminate. The devices comprise 25 mg ofchamomile oil and 25 mg of chlorophyll and are used, for example, forthe treatment of pressure sores and chafed sites.

EXAMPLE 13

20 parts of pantothenyl alcohol are melted at 90° C. 21 parts of sodiumcarboxymethyl starch and 2 parts of a glycolic extract of fucusvesicolosus are stirred into the melt up to an even distribution (meltA).

30 parts of hydroabietyl alcohol, 15 parts of anethyl-vinyl-acetate-copolymer having a vinyl acetate content of 28%, 10parts of a polyalkadiene having the monomer chain length C4 to C5, 1part of ethylcellulose, and 1 part of vitamin E are melted separately at125° C. (melt B).

Melt B is cooled to 90° C. under stirring and slowly stirred into melt Aat 90° C. up to an even distribution. Then, the pressure sensitivehot-melt adhesive is spread on a siliconized polyester sheet at a massper unit area of 300 g/m² by means of knife coating. After cooling, apolyurethane sheet is laminated thereon. Devices having a surface of 10cm² are punched from the laminate. The devices comprise 6 mg of fucusextract and 3 mg of vitamin E; they are used, for example, for thetopical treatment of skin areas damaged by exposure to the sun or byenvironmental toxicants in order to bind moisture in the skin and toachieve an effective cell protection against external influences.

EXAMPLE 14

20 parts of pantothenyl alcohol are melted at 90° C. 10 parts ofglycerol and 1 part of ethylcellulose are slowly stirred into the meltuntil an even distribution results (melt A).

18 parts of gelatin, 10 parts of polyvinylpyrrolidone, 5 parts of sodiumcarboxymethyl starch, 10 parts of saccharose, 3 parts of tincture ofarnica, and 3 parts of calendula tincture are made into a paste at roomtemperature using 20 parts of water, intensively homogenized until auniform distribution is achieved, and then heated to 90° C. understirring (melt B).

At 90° C., melt B is slowly stirred into melt A up to an evendistribution. The pressure sensitive hot-melt adhesive is then spread ona siliconized paper composite at a mass per unit area of 400 g/m² bymeans of knife coating; after cooling, a polyester sheet is laminatedthereon. Devices of 50 cm² are punched from the laminate; they comprise60 mg of arnica tincture and 60 mg of calendula tincture. The devicesare used, for example, for the intradermal treatment of sprains,contusions, and haemorrhages.

EXAMPLE 15

19 parts of pantothenyl alcohol are melted at 90° C. 8 parts of glyceroland 4 parts of ethylcellulose are slowly stirred into the melt until aneven distribution results (melt A).

At room temperature, 20 parts of gelatin, 10 parts ofpolyvinylpyrrolidone, 5 parts of sodium carboxymethyl starch, 9 parts ofsaccharose, and 5 parts of an aqueous extract of green tea are made intoa paste using 20 parts of water, intensively homogenized until a uniformdistribution is achieved, and then heated to 90° C. under stirring (meltB).

At 90° C., melt B is slowly stirred into melt A up to an evendistribution. Then, the pressure sensitive hot-melt adhesive is spreadon a siliconized polyester sheet at a mass per unit area of 400 g/m² bymeans of knife coating; after cooling, a polyurethane sheet is laminatedthereon. Devices having an area of 100 cm² are punched from thelaminate. The devices comprise 20 mg of tea extract; when applied to theskin they are used to a achieve a stimulating effect on the circulatorysystem by the transdermal release of caffeine, which is the maincomponent of the extract.

EXAMPLE 16

20 parts of pantothenyl alcohol are melted at 90° C. 10 parts ofglycerol, 1 part of ethylcellulose, and 5 parts of hop extract areslowly stirred into the melt until an even distribution results (meltA).

18 parts of gelatin, 10 parts of polyvinylpyrrolidone, 5 parts of sodiumcarboxymethyl starch, and 11 parts of saccharose are made into a pasteat room temperature using 20 parts of water, intensively homogenizeduntil a uniform distribution is achieved, and then heated to 90° C.under stirring (melt B).

At 90° C., melt B is slowly stirred into melt A up to an evendistribution. The pressure sensitive hot-melt adhesive is then spread ona siliconized paper composite at a mass per unit area of 300 g/m² bymeans of knife coating and temporarily covered with a siliconizedHDPE-sheet.

Separately, a second hydrophilic pressure sensitive hot-melt adhesive ismanufactured in accordance with the above formulation; instead of hopextract, it contains 5 parts of valerian extract. After spreading on asiliconized paper composite and cooling, this hydrophilic pressuresensitive hot-melt adhesive is laminated on the pressure sensitivehot-melt adhesive comprising the hop extract; prior to that thetemporary HDPE-sheet is stripped off. After removal of the siliconizedpaper composite from the valerian-extract-layer, a polyurethane layer islaminated on this layer.

Devices with an area of 30 cm² are punched from this multi-layercomposite; they comprise 45 mg of hop extract in the pressure sensitivehot-melt adhesive facing the protective layer, and 45 mg of valerianextract in the pressure sensitive hot-melt adhesive facing the backinglayer.

When applied to the skin, these devices are used to achieve a calmativeeffect, for example, in stress situations, by the transdermal release ofthe sedative components of the valerian and hop.

EXAMPLE 17

24 parts of pantothenyl alcohol are melted at 90° C. 10 parts ofglycerol and 2 parts of ethylcellulose are slowly stirred into the meltuntil a uniform distribution results (melt A).

18 parts of sodium alginate, 10 parts of polyvinylpyrrolidone, 5 partsof sodium carboxymethyl starch, and 11 parts of saccharose are made intoa paste at room temperature using 20 parts of water, intensivelyhomogenized until a uniform distribution is achieved, and then heated to90° C. under stirring (melt B).

At 90° C., melt B is slowly stirred into melt A up to an evendistribution. The pressure sensitive hot-melt adhesive is then spread ona siliconized paper composite at a mass per unit area of 200 g/m² bymeans of knife coating; after cooling a siliconized HDPE intermediatecover is laminated thereon. The composite is cut such that narrow rollshaving a width of 13 cm are obtained. The intermediate cover is removedfrom such a narrow roll, and a mixture comprising 1 ml of eucalyptus oiland 1 of ml pine-needle oil is applied on the pressure sensitivehot-melt adhesive in a dotlike manner on areas of 6×13 cm. After removalof the intermediate cover, a second hydrophilic pressure sensitivehot-melt adhesive having a width of 13 cm is laminated on said layer.After removal of one of the siliconized paper protective layers, amicroporous polyester backing layer is laminated.

Devices of 6×13 cm are punched and sealed tightly. After uniformdistribution of the essential oils in the pressure sensitive hot-meltadhesive by means of diffusion, the device may be used for colds, e.g.,by sticking it on the skin in the upper chest region. When the device isheated to body temperature, the essential oils which are released viathe micro-porous backing layer and are then inhaled can develop theiralleviating effect.

What is claimed is:
 1. A self-adhesive product for application to intactskin which comprises a water-free pressure sensitive adhesive for therelease of a substance to or through the skin, and a substance to bereleased, said substance being distributed within said pressuresensitive adhesive, wherein said pressure sensitive adhesive is apressure sensitive hot-melt adhesive prepared by melt mixing at atemperature of between 40 and 150° C. a mixture comprising at least onewater-soluble or water-swellable polymer, and at least one water-solublemeltable adhesive resin.
 2. A product according to claim 1, wherein saidsubstance is uniformly distributed within said pressure-sensitiveadhesive.
 3. A product according to claim 1, wherein said substance isnon-uniformly distributed within said pressure-sensitive adhesive.
 4. Aproduct according to claim 1, wherein the pressure-sensitive hot-meltadhesive comprises water-soluble, ropy, low-viscous tacky substance incombination with hydrophilic polymer forming coherent layers ofexcellent cohesion.
 5. A product according to claim 1, wherein thepressure-sensitive hot-melt adhesive is hydrophilic and comprises atleast one water-soluble or water-swellable polymer and at least onewater-soluble, meltable adhesive resin.
 6. A product according to claim1, wherein the pressure sensitive hot-melt adhesive is hydrophilic andis melt mixed at a temperature between 80 and 120° C.
 7. A productaccording to claim 1, wherein the water-soluble meltable adhesive resincomponent is pantothenyl alcohol, honey, a low-molecular weight sugar,an ester of a low-molecular weight sugar or mixtures thereof.
 8. Aproduct according to claim 1, wherein the pressure-sensitive adhesivehot-melt adhesive is hydrophilic and contains, as water-soluble orwater-swellable polymer, at least one member of the group consisting ofgelatin, sodium alginate, pectin, carrageenan, xanthan, cellulosederivatives, starch and starch derivatives, galactomannan andgalactomannan derivatives, polyvinyl alcohol, polyvinylpyrrolidone,vinyl-pyrrolidone-vinyl-acetate copolymers, polyethylene glycols andpolypropylene glycols.
 9. A product according to claim 1, wherein thesubstance to be released is acetylsalicylic acid.
 10. A productaccording to claim 1, wherein the substance to be released is a steroidhormone.
 11. A product according to claim 1, wherein a eutectic mixtureof lidocaine and prilocaine is the substance to be released.
 12. Aproduct according to claim 1, wherein at least one vegetable preparationis the substance to be released.
 13. A product according to claim 12,wherein the vegetable preparation is an extract or tincture.
 14. Aproduct according to claim 1, wherein a triturated plant portion is thesubstance to be released.
 15. A product according to claim 14, whereinthe triturated plant portion is tobacco powder.
 16. A product accordingto claim 1, wherein the pressure-sensitive hot-melt adhesive ishydrophilic and comprises a lipophilic phase.
 17. A product according toclaim 1, wherein the pressure-sensitive hot-melt adhesive is hydrophilicand comprises at least one adjuvant selected from the group consistingof humectants, softening agents, penetration enhancers, preservatives,disinfectants, pH-regulators, antioxidants, active substancestabilizers, emulsion stabilizers, odorous substances, dyes, inertfillers, oils, fats, and waxes.
 18. A product according to claim 1,comprising a flexible backing layer, an active substance-containing,hydrophilic pressure-sensitive hot-melt adhesive connected thereto, inthe absence of other controlling mechanisms a membrane controlling therelease of the substances, optionally a pressure-sensitive adhesivemeans connected to the membrane for the fixation of the product to theskin, and a protective layer which covers an adhesive surface of theproduct facing the skin and which is removed prior to the application ofthe product.
 19. A product according to claim 18, wherein the backinglayer is permeable to highly volatile substances.
 20. A productaccording to claim 1, wherein the pressure-sensitive hot-melt adhesiveis hydrophilic and has a porous structure.
 21. A product according toclaim 1, wherein the substance-releasing portion has a multi-layer ormulti-part structure wherein the individual layers or parts have thesame or different composition.
 22. A product according to claim 1,wherein the product is at least partially biodegradable.
 23. A method ofusing a product according to claim 1, which comprises applying saidproduct to the skin of a human or animal.
 24. A method of using aproduct according to claim 1, which comprises applying said product to aplant.